Science Liver Battlefield – The Difference Between Immunity and Metabolism in Men and Women

Scientists at the University of California, San Francisco (UCSF) have developed a new approach based on evolutionary biology to study sexist diseases
.
Their theory is that men and women choose opposite paths
in the trade-off between immunity and metabolism in the liver.
This helps males fight bacterial infections injured in battles for superiority, while helping females store subcutaneous fat to survive
in times of food shortages.
Through studies in mice, the scientists characterized the activity of a signaling pathway that regulates lipids that stores fat in the livers of male mice and releases it into the bloodstream
of female mice.
This pathway also responds
to growth hormone.

This phenomenon may shape male physiology and is risky
in today's high-calorie environment.
These findings are particularly relevant for fatty liver, which affects a quarter of the U.
S.
population
.
It occurs mainly in men until women enter menopause
.

Dr Holly Ingraham, Hertzstein Professor of Molecular Physiology at the University of California, San Francisco, said: "Scientists have only recently begun to understand that there are these profound differences
between men and women.
" The study was published in the journal Science on October 21, 2022
.
"Understanding these differences will be key
to unlocking treatments for sexist diseases.
" Fatty liver is an example
.
”

Experiments have found that male mice infected with E.
coli have three times the
survival rate of female mice.
Females developed hyperlipidemia, which can also occur
in humans with severe sepsis.
Lowering their lipid levels helps them survive
.

The researchers then studied the responses
of male and female mice to the contemporary environmental challenge of overeating by feeding them high-fat foods.
Males develop fatty liver and glucose intolerance, which can lead to type 2 diabetes, but females do not
.
This is true
even if the male and female gain similar weight.

In their search for literature that could explain this phenomenon, the team found a transcription factor called BCL6, which prevents lipolysis in the liver and is more present
in male mice.
The gene that deletes this protein eliminates liver fat in males, while also eliminating their ability to
survive an infection.

"Host defense programs in the liver are predisposing factors for fatty liver in men," said Joni Nikkanen, Ph.
D.
, a postdoc in the Department of Cellular Molecular Pharmacology, who began the research with Dr.
Ajay Chawla, who was previously at UCSF and now at Merck Research Laboratories
.

"We have evolved to explain why there are programs like this – because they protect males from bacterial infections
," he said.
But in another case, these same items are no longer good for you, and you will develop a more serious fatty liver
.
”

The team also looked at how the presence of BCL6 affects gene expression
in the liver.
This process begins during puberty, when males produce more testosterone and their pituitary gland begins to secrete growth hormone, with spikes and valleys
.

These intermittent bursts are most likely regulated by testosterone and are very important
.
When the researchers continuously injected growth hormone into male mice in the same way that female mice secreted growth hormone, BCL6 disappeared from their livers and they lost their ability to
fight E.
coli infection.

The findings suggest that growth hormone may be a potential therapy for fatty liver disease in adults, an idea that is currently being
tested.
Its effects have been well demonstrated
in children whose pituitary gland does not produce enough growth hormone.
Male children are especially prone to fatty liver, but when they take growth hormone to treat their short stature, the fatty liver disappears
.
The work also expands the scientific view of how the body fights infections to include organs such as the liver
.

"The battle is still between infection and the immune system," said
study co-author Dr.
Omer Gokcumen.
"But the liver dominates the battlefield
.
"

An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice